Anticipation is running high as scientists around the world race to develop a vaccine for Covid-19 . Some vaccines showed very promising results in early data. But a vaccine is a highly complicated drug that works on the human body’s complex immune system. We will walk you through the issues to explain how the drug and the human body work, and why a vaccine may not work at all. What is the immune system? It is a complex system of cells, organs and processes that detect foreign substances, including bacteria, viruses, parasites and transplanted organs. The human body counts on the system to detect and identify the foreign substances then develop layers of defence against them. How does the immune system work? When germs such as bacteria or viruses invade the body, they multiply, causing infection and possible illness. The body can mount a non-specific attempt – called an innate response – to try to eliminate the invaders within hours of an infection. Infections that can be quickly resolved by innate response may not produce symptoms. When an innate response fails to contain an infection, adaptive response is mounted, usually days later, to fight off the invasion with the help of white blood cells: T-cells and B-cells. Some types of T-cells identify and kill infected cells. Some help B-cells make antibodies, a kind of protein. A specific type of antibody, called a neutralising antibody, binds to a pathogen and blocks it from entering human cells, thus stopping infection, in a process known as neutralising. It is all right for the number of antibodies to decline after a disease is cured, thanks also to T-cells and B-cells. The so-called memory B-cells and T-cells stored in the body can remember the infection and stand by to fight off a similar invasion in future. How does a vaccine work? Vaccines train the immune system to develop a response by mimicking an infection. The process may cause symptoms such as fever, but it also prompts the human body to produce T-cells and antibodies. When the mock infection is over, the body is left with memory T-cells and B-cells that hopefully can remember the infection and mount a defence immediately in the face of a real threat. How do the Covid-19 vaccines work? Scientists around the world are trying to develop vaccines against Sars-CoV-2 – the official name of the coronavirus that causes the disease Covid-19 – using differing technologies. Three Chinese developers have used a traditional method by producing vaccines after killing the virus first. Some vaccine candidates (such as Chinese firm CanSino and Oxford University ) use genetically engineered adenovirus as a vector to deliver the gene that encodes the spike protein of Sars-CoV-2 into human cells. The spike protein on the surface of Sars-CoV-2 binds to human cells as its means of invasion. Some vaccine candidates (such as Moderna in the US) use technologies that have never been licensed in vaccines before, by using the platform of nucleic acid and also targeting the S protein. The largest group of candidates use immune-stimulating viral protein antigens. Are Covid-19 vaccine candidates working? Candidates for which data has been published have been shown to induce neutralising antibodies against the spike protein. But whether they offer real protection can be discovered only after large-scale phase 3 trials, which test the broader safety and efficacy of a vaccine. First Covid-19 vaccines due early 2021, but can they deliver as promised? Another important question is what type of protection we want to achieve,” Florian Krammer, professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York, said last Thursday. “Do we want protection from infection, which is really hard to do? Do we want protection from the disease, or protection from severe disease? I want to put this out there, because there have been a lot of different expectations and a lot of people want to see protection from infection but may not realise how hard it is.” Will Covid-19 vaccines produce lasting immunity? Some vaccines produce longer “memories” than others. Immunity gained from vaccines could wear off in a few years and require booster doses. So far, the duration of immunity achieved by Covid-19 vaccine candidates is unknown, and would need to be studied in a large-scale trial. “You need time to see whether things last a long time, but there are immunological indications that immune memory may be developed,” Dr Naor Bar-Zeev, associate professor with Johns Hopkins Bloomberg School of Public Health, said. “The vaccines, at least the adenovirus-vectored ones, reported T-cell responses. And that is really great, because T-cells not only provide a broad response but potentially provide immunological memory. We'll have to see how that pans out, but that’s a good indication.” What does shorter immunity duration mean for those who plan to take Covid-19 vaccine shots? A vaccine may be effective for only six months. “There’s a real ethical question about distribution and the sources, and what it would take to vaccinate a whole population, then vaccinate them again – it becomes infeasible,” Bar-Zeev said. “We may very well have a vaccine that's suboptimal.” How far are we from a Covid-19 vaccine? Six vaccine candidates are in phase 3 human trials, with some of their makers promising delivery by later this year. A total of 26 vaccines are in various phases of trials and 139 are under preclinical study, according to the World Health Organisation last month. US study says suppressing immune response could help fight Covid-19 Are we guaranteed a vaccine? Krammer said he still needed to see data from phase 3 trials but felt that a vaccine offering “protection from disease is quite realistic”. However, history shows no shortage of vaccines that appeared promising only to flop at phase 3. For Covid-19, low efficacy would rule out a vaccine candidate. “If you see a 20 per cent efficacy, I don’t think that would go forward,” Krammer said. There is also the issue of severe adverse events that can show up when trial scale is expanded from dozens to thousands of people. “Neurological issues or autoimmune disease, I think something like that could kill a vaccine’s chances relatively quickly,” he said.